Cell reports (Cambridge), 2016-05, Vol.15 (9), p.2000-2011
2016
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- Autor(en) / Beteiligte
- Titel
- Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
- Ist Teil von
- Cell reports (Cambridge), 2016-05, Vol.15 (9), p.2000-2011
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming TAM populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, FcγRIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment. [Display omitted] •Scavenger receptor MARCO is expressed by suppressive tumor-associated macrophages•Antibody targeting of MARCO-expressing TAMs blocks tumor growth and metastasis•Anti-MARCO enhances the effect of checkpoint therapy in melanoma and colon carcinoma•MARCO is expressed on TAMs in human breast cancer and metastatic melanoma Georgoudaki et al. show that tumor-associated macrophages can be targeted using an antibody toward the pattern recognition receptor MARCO. This results in altered macrophage polarization and a reduction in tumor growth and metastasis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2016.04.084Titel-ID: cdi_doaj_primary_oai_doaj_org_article_cc3f009b26304544ac716a2b2776c512
- Format
- –
- Schlagworte
- Animals, Antibodies, Neoplasm - pharmacology, Biomarkers, Tumor - metabolism, Breast Neoplasms - immunology, Breast Neoplasms - pathology, Breast Neoplasms - therapy, Cell Polarity - drug effects, Cell Proliferation - drug effects, Cytokines - pharmacology, Disease Progression, Epithelial-Mesenchymal Transition - drug effects, Female, Humans, Immunosuppression, Immunotherapy, Macrophages - metabolism, Medicin och hälsovetenskap, Melanoma - immunology, Melanoma - pathology, Melanoma - therapy, Mice, Neoplasm Metastasis, Neoplasms - immunology, Neoplasms - pathology, Neoplasms - therapy, Receptors, IgG - metabolism, Receptors, Immunologic - metabolism, Stromal Cells - pathology, Tumor Microenvironment - drug effects, Tumor Microenvironment - immunology